Candida biofilms: is adhesion sexy?

The development of Candida albicans biofilms requires two types of adhesion molecule - the Als proteins and Hwp1. Mutational analyses have recently revealed that these molecules play complementary roles, and their characteristics suggest that they may have evolved from primitive mating agglutinins.     

Granulocyte adhesion molecules — structure/functionrelationships

Neutrophil responses are regulated by cellular adhesion events, including interaction with. extracellular matrix and other cell types. The diversity of molecular structures which are included in the repertoire of cell adhesion molecules expressed by neutrophils and their subtle regulation allow fine tuning of cell adhesion processes to suit environmental demands. This article reviews some of the recent findings using biochemical, immunochemical and molecular techniques that allow the relationship between adhesion molecule structure and function to be examined. Understanding the molecular basis of cell adhesion events will allow development of novel strategies that allow manipulation of adhesion processes in a clinical setting.     

Elevated ZIPK is required for TNF-α-induced cell adhesion molecule expression and leucocyte adhesion in endothelial cells

Leucocyte adhesion to the vascular endothelium is a critical event in the early inflammatory response to infection and injury.This process is primarily regulate...     

Potassium channel gating in adhesion: from an oocyte–silicon to a neuron–astrocyte adhesion contact

In a neuron–astrocyte adhesion contact the ionic current due to the opening of voltage-dependent potassium channels has to flow along a narrow intercellular cleft, generating there an extracellular voltage. This voltage might be large enough to affect significantly the dependence of channel gating from the intracellular voltage. In order to test this hypothesis, we considered a Xenopus oocyte expressing voltage-dependent potassium channels adhering to a layer of silicon oxide as a simplified model of cell–cell adhesion; here the cell membrane and silicon oxide are separated by a narrow cleft and form a junction of circular shape. We measured directly the extracellular voltage along the diameter of the cleft and investigated its effect on channel gating using a linear array of field effect transistors integrated in the silicon substrate. On this experimental basis we demonstrated that the voltage dependence of potassium channels is strongly affected by adhesion, as can be predicted using a model of a two-dimensional cable and electrodiffusion theory. Computations based on the model showed that along a neuron–astrocyte adhesion contact the opening of voltage-dependent Kv2.1 potassium channels is significantly reduced with respect to identical channels facing an open extracellular space.     

Integrin clipping: A novel adhesion switch?

During human prostate cancer progression, the majority of normally expressed integrins are suppressed with the exception of the alpha6, alpha3, and beta1 integrins. We have shown that in prostate cancer, the alpha6 integrin is found paired with the beta1 integrin and that a novel form of the alpha6 integrin that lacks a large portion of the extracellular domain (alpha6p) exists. The alpha6pbeta1 integrin is found in human prostate cancer tissue specimens as well as tissue culture cell lines and is formed on the cell surface. This review discusses the mechanism of alpha6pbeta1 production and the potential functions of this integrin variant. Our current working model predicts that the alpha6pbeta1 integrin maintains the intracellular cytoskeletal connections associated with the heterodimer while allowing for an alteration in cell adhesion. The mechanism provides a selective advantage for cancer cell metastasis.     

Troglitazone, a PPAR-γ activator prevents endothelial cell adhesion molecule expression and lymphocyte adhesion mediated by TNF-α

Background  

Cytokine mediated induction of the mucosal addressin cell adhesion molecule-1(MAdCAM-1) expression is associated with the onset and progression of inflammatory bowel disease (IBD).     

Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation

Focal adhesions undergo myosin-II-mediated maturation wherein they grow and change composition to modulate integrin signalling for cell migration, growth and differentiation. To determine how focal adhesion composition is affected by myosin II activity, we performed proteomic analysis of isolated focal adhesions and compared protein abundance in focal adhesions from cells with and without myosin II inhibition. We identified 905 focal adhesion proteins, 459 of which changed in abundance with myosin II inhibition, defining the myosin-II-responsive focal adhesion proteome. The abundance of 73% of the proteins in the myosin-II-responsive focal adhesion proteome was enhanced by contractility, including proteins involved in Rho-mediated focal adhesion maturation and endocytosis- and calpain-dependent focal adhesion disassembly. During myosin II inhibition, 27% of proteins in the myosin-II-responsive focal adhesion proteome, including proteins involved in Rac-mediated lamellipodial protrusion, were enriched in focal adhesions, establishing that focal adhesion protein recruitment is also negatively regulated by contractility. We focused on the Rac guanine nucleotide exchange factor β-Pix, documenting its role in the negative regulation of focal adhesion maturation and the promotion of lamellipodial protrusion and focal adhesion turnover to drive cell migration.     

Gastrulation in zebrafish — all just about adhesion?

During vertebrate gastrulation, the evolutionarily conserved morphogenetic movements of epiboly, internalization, convergence and extension cooperate to generate germ layers and to sculpt the body plan. In zebrafish, these movements are driven by a variety of cell behaviors, including slow and fast directed migration, radial and mediolateral intercalation, and cell shape changes. Whereas some signaling pathways are required for a subset of these behaviors, other molecules, such as E-cadherin or Galpha12 and Galpha13 proteins, appear to have a widespread role in different gastrulation cell behaviors.     

Fibronectin–collagen binding and requirement during cellular adhesion

Fibronectin isolated from human plasma and from the extracellular matrices of cell monolayers mediates the attachment in vitro and spreading of trypsin-treated cells on a collagen substratum. Fibronectin-dependent kinetics of cellular attachment to collagen were studied for several adherent cell types. It was shown that trypsin-treated human umbilical-cord cells, mouse sarcoma CMT81 cells, endothelial cells, and human fibroblasts from a patient with Glanzmann's disease were completely dependent on fibronectin for their attachment to collagen, whereas guinea-pig and monkey smooth-muscle cells and chick-embryo secondary fibroblasts displayed varying degrees of dependence on fibronectin for their attachment. Radiolabelled human plasma fibronectin possessed similar affinity for collagen types I, II and III from a variety of sources. The fibronectin bound equally well to the collagens with or without prior urea treatment. However, in the fibronectin-mediated adhesion assay using PyBHK fibroblasts, a greater number of cells adhered and more spreading was observed on urea-treated collagen. Fibronectin extracted from the extracellular matrix of chick-embryo fibroblasts and that purified from human plasma demonstrated very similar kinetics of complexing to collagencoated tissue-culture dishes. Fibronectin from both sources bound to collagen in the presence of 0.05–4.0m-NaCl and over the pH range 2.6–10.6. The binding was inhibited when fibronectin was incubated with 40–80% ethylene glycol, the ionic detergents sodium dodecyl sulphate and deoxycholate, and the non-ionic detergents Nonidet P-40, Tween 80 and Triton X-100, all at a concentration of 0.1%. From these results we proposed that fibronectin–collagen complexing is mainly attributable to hydrophobic interactions.     

Integration of cell adhesion reactions--a balance of forces?

The rearrangement of receptors by oligomeric adhesion molecules constitutes a configurational mechanism able to sculpture membranes and dislocate receptors from cytoplasmic anchorage. This provides a conceptual framework for complex cellular processes in mechanical terms, as a dynamic balance between extracellular and intracellular driving forces.     

Endothelial cell–cell adhesion during zebrafish vascular development

The vertebrate vasculature is an essential organ network with major roles in health and disease. The establishment of balanced cell–cell adhesion in the endothelium is crucial for the functionality of the vascular system. Furthermore, the correct patterning and integration of vascular endothelial cell–cell adhesion drives the morphogenesis of new vessels, and is thought to couple physical forces with signaling outcomes during development. Here, we review insights into this process that have come from studies in zebrafish. First, we describe mutants in which endothelial adhesion is perturbed, second we describe recent progress using in vivo cell biological approaches that allow the visualization of endothelial cell–cell junctions. These studies underline the profound potential of this model system to dissect in great detail the function of both known and novel regulators of endothelial cell–cell adhesion.     

A hot water extract of Curcuma longa inhibits adhesion molecule protein expression and monocyte adhesion to TNF-α-stimulated human endothelial cells

The recruitment of arterial leukocytes to endothelial cells is an important step in the progression of various inflammatory diseases. Therefore, its modulation is thought to be a prospective target for the prevention or treatment of such diseases. Adhesion molecules on endothelial cells are induced by proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), and contribute to the recruitment of leukocytes. In the present study, we investigated the effect of hot water extract of Curcuma longa (WEC) on the protein expression of adhesion molecules, monocyte adhesion induced by TNF-α in human umbilical vascular endothelial cells (HUVECs). Treatment of HUVECs with WEC significantly suppressed both TNF-α-induced protein expression of adhesion molecules and monocyte adhesion. WEC also suppressed phosphorylation and degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) induced by TNF-α in HUVECs, suggesting that WEC inhibits the NF-κB signaling pathway.     

Optimal intensity shock wave promotes the adhesion and migration of rat osteoblasts via integrin β1-mediated expression of phosphorylated focal adhesion kinase

To search for factors promoting bone fracture repair, we investigated the effects of extracorporeal shock wave (ESW) on the adhesion, spreading, and migration of osteoblasts and its specific underlying cellular mechanisms. After a single period of stimulation by 10 kV (500 impulses) of shock wave (SW), the adhesion rate was increased as compared with the vehicle control. The data from both wound healing and transwell tests confirmed an acceleration in the migration of osteoblasts by SW treatment. RT-PCR, flow cytometry, and Western blotting showed that SW rapidly increased the surface expression of α5 and β1 subunit integrins, indicating that integrin β1 acted as an early signal for ESW-induced osteoblast adhesion and migration. It has also been found that a significant elevation occurred in the expression of phosphorylated β-catenin and focal adhesion kinase (FAK) at the site of tyrosine 397 in response to SW stimulation after the increasing expression of the integrin β1 molecule. When siRNAs of integrin α5 and β1 subunit were added, the level of FAK phosphorylation elevated by SW declined. Interestingly, the adhesion and migration of osteoblasts were decreased when these siRNA reagents as well as the ERK1/2 signaling pathway inhibitors, U0126 and PD98059, were present. Further studies demonstrated that U0126 could inhibit the downstream integrin-dependent signaling pathways, such as the FAK signaling pathway, whereas it had no influence on the synthesis of integrin β1 molecule. In conclusion, these data suggest that ESW promotes the adhesion and migration of osteoblasts via integrin β1-mediated expression of phosphorylated FAK at the Tyr-397 site; in addition, ERK1/2 are also important for osteoblast adhesion, spreading, migration, and integrin expression.     

Integrin adhesion: when is a kinase a kinase?

Recent genetic studies in the worm Caenorhabditis elegans and fruitfly Drosophila have revealed the essential role integrin-linked kinase plays in integrin adhesion - but it apparently acts in this role as an adaptor rather than a kinase.     

Chicken lactose lectin: Cell-to-cell or cell-to-matrix adhesion molecule?

Summary Endogenous chicken muscle lectin isolated by lactose affinity chromatography inhibits myoblast fusion. Similar lectins isolated from embryonic brain, heart, and liver and from adult intestine exhibit the same ability. Elevated levels of any of these lectins canceled the inhibitory effect. Peanut agglutinin isolated by the same procedure had no effect at any concentration tested. Concanavalin A affected fusion only at high concentrations. Muscle lectin was shown to agglutinate myoblasts in microtiter plates, whereas exogenous addition in culture inhibited alignment as seen by time lapse microcinematography. Cell-to-cell communication between lectin-treated cells was shown by nucleotide exchange, and lectin-coated culture dishes did not affect cell attachment. Our evidence shows a lack of specificity to muscle, but suggests an aggregating capacity between cells, or possibly an interaction between the cell membrane and the extracellular matrix. This study was supported by National Institutes of Health grants AM 25202 and HD 07104, The Muscular Dystrophy Association, and the Cleveland chapter of Sigma Xi.     

Interleukin 32 (IL-32) contains a typical α-helix bundle structure that resembles focal adhesion targeting region of focal adhesion kinase-1

IL-32 can be expressed in several isoforms. The amino acid sequences of the major IL-32 isoforms were used to predict the secondary and tertiary protein structure by I-TASSER software. The secondary protein structure revealed coils and α-helixes, but no β sheets. Furthermore, IL-32 contains an RGD motif, which potentially activates procaspase-3 intracellular and or binds to integrins. Mutation of the RGD motif did not result in inhibition of the IL-32β- or IL-32γ-induced cytotoxicity mediated through caspase-3. Although IL-32α interacted with the extracellular part of αVβ3 and αVβ6 integrins, only the αVβ3 binding was inhibited by small RGD peptides. Additionally, IL-32β was able to bind to αVβ3 integrins, whereas this binding was not inhibited by small RGD peptides. In addition to the IL-32/integrin interactions, we observed that IL-32 is also able to interact with intracellular proteins that are involved in integrin and focal adhesion signaling. Modeling of IL-32 revealed a distinct α-helix protein resembling the focal adhesion targeting region of focal adhesion kinase (FAK). Inhibition of FAK resulted in modulation of the IL-32β- or IL-32γ-induced cytotoxicity. Interestingly, IL-32α binds to paxillin without the RGD motif being involved. Finally, FAK inhibited IL-32α/paxillin binding, whereas FAK also could interact with IL-32α, demonstrating that IL-32 is a member of the focal adhesion protein complex. This study demonstrates for the first time that IL-32 binds to the extracellular domain of integrins and to intracellular proteins like paxillin and FAK, suggesting a dual role for IL-32 in integrin signaling.